The importance of early detection of cancer for improving the patients' quality of life (QOL) has been pointed out in recent years. For example, according to a graph on 5-year survival rate of stomach cancer cases, the survival rate of patients whose stomach cancer is detected in the initial stage (first stage) is 90%. By contrast, the survival rate of the end stage (fourth stage) stomach cancer patients is less than 10%. This demonstrates the high importance of early diagnosis of cancer in patients for the current therapy. Also because of frequent lack of subjective symptom of primary cancer, it is necessary to give cancer diagnosis to quite healthy people, in order to ensure the early detection. For this purpose, development of non-invasive and safe method of the diagnosis is desired.
From the viewpoint of non-invasiveness and safety, utilization of MRI (magnetic resonance imaging) appears recommendable, as it uses magnetic field or radio waves and is free of fear of exposure to radiation. However, the present state of art is still unable to detect primary cancer with MRI. Many and various contrast agents in forms easy of handling are being proposed, with the view to obtain still higher contrast to raise sensitivity of MRI (for example, see the Non-patent References 1, 2 and 3 in the collective listing given later, and so forth). While these contrast agents include actually widely used excellent contrast agents such as Gd-DTPA (gadodiamide), it may worth continual investigations if further improvements are possible.
On the other hand, we have developed a drug delivery system using specific block copolymers and succeeded in offering certain anti-cancer drug with increased tumor tissue-selective accumulation, whose favorable therapeutic effect has been clinically confirmed.
Furthermore, there was a method proposed in the past as a means to introduce DNA into cells, which used a complex formed by making use of the property of calcium phosphate (hydroxyapatite) crystals to bind to DNA, the crystals being formed when an aqueous calcium solution and aqueous phosphoric acid solution were mixed to bring about oversaturated condition. A part of us discovered that, in the attempt to improve the disadvantage incidental to the method, the calcium phosphate particles could be formed with controlled size, when incubated with the specific block copolymer containing a hydrophilic, nonionic polyethylene glycol (PEG) segment and a polyanionic segment derived from carboxyl group. We furthermore confirmed that the so obtained particles had not only relatively narrow particle size distribution and that their average particle size could be controlled to be less than submicron order (several hundreds nm) where necessary, but also aqueous dispersion systems containing these particles could be stably stored under ambient conditions, without inducing sedimentation. In consequence, we proposed a novel organic-inorganic hybrid particle system which could carry, as the drug, DNA or other bioactive substances and deliver the drug to cancer tissues or cancer cells (see Patent Reference 1).